BACKGROUND.Bexarotene is one of the most active single agents for the treatment of recurring or refractory cutaneous T‐cell lymphoma (CTCL). Interferon alfa has also been used for many years as an effective treatment for this disease. The results in recent case reports of the combination of bexarotene and interferon alfa have been promising. Based on more extensive results reported with the combination of other retinoids with interferon alfa, the present study attempted to determine the response rate, response duration, and safety of bexarotene (Targretin capsules, Ligand Pharmaceuticals, San Diego, Calif) alone and then with the addition of interferon alfa‐2b (Intron‐A, Schering‐Plough, Kenilworth, NJ).METHODS.Patients with biopsy‐proven CTCL, TNM stages IB, IIA, IIB‐IV, were treated with oral bexarotene 300 mg/m2/day for at least 8 weeks. If a complete response was not seen after 8 weeks, interferon alfa‐2b 3 million units (MU) subcutaneously was added, and increased to 5 MU if tolerated, 3 times a week.RESULTS.A total of 22 patients were enrolled at 5 sites, and 18 patients were assessable for response. Overall response rate for combined bexarotene and interferon alfa was 39% (95% confidence interval [CI]: 17%–64%), including 1 patient with a clinical complete response, 6 patients with partial response, 3 patients with stable disease, and 8 patients with progressive disease. Three partial responses were first noted during the bexarotene‐alone phase. Adverse events were generally manageable, and only 1 patient was withdrawn from study for hypertriglyceridemia.CONCLUSIONS.The addition of interferon alfa‐2b did not increase the response rate that would have been expected with bexarotene alone. Cancer 2007. © 2007 American Cancer Society.

Bexarotene, a synthetic retinoid ligand for the retinoid X receptor (RXR), is a highly active agent in the treatment of relapsed or refractory CTCL with a response rate of ~45% (Arch Dermatol137: 581–93, 2001; J Clin Oncol19: 2456–71, 2001). Interferon alfa has a similar response rate although the doses and responses in the literature have varied. Promising results have been reported with combinations of retinoids and interferon alfa, including bexarotene (J Am Acad Dermatol50: 375–9, 2004). To explore this combination, a phase II trial was designed in which patients with CTCL were treated with bexarotene 300 mg/m2/day for at least 8 weeks. If less than a complete response was seen at this time, interferon alfa-2b at a dose of 3 million units escalated to 5 million units subcutaneously 3 times weekly was added for another 8 weeks. Responding patients could continue treatment beyond 16 weeks. Twenty-two patients with CTCL were enrolled in the trial: median age 58 years (22–79); 9 males, 13 females, TNM stages: IB (3), II (7), III (4), IV (8). One patient had no prior treatment; the rest had relapsed or refractory disease with a mean of 49 months from initial diagnosis to enrollment. Four patients had previously received bexarotene and 2 interferon alfa. Seventeen patients completed 16 weeks of treatment and are assessable for response, 1 has not completed 16 weeks and 4 received less than 16 weeks (1 early death, 1 non-compliant, 1 withdrawal of consent because of side effects, and 1 myocarditis, probably not treatment-related). Using reproducible objective criteria for response utilized in the single agent bexarotene trials cited above (Primary Endpoint Classification), 6 of 17 patients achieved a partial response and 1 a complete response (objective response rate 41%, 95% confidence intervals 18%–67%). Three of the 6 partial responses occurred with bexarotene alone at 8 weeks. Median duration of response was 2.7 months, range 1.1–7.6 months. Reversible grade 3 or 4 toxicities seen in more than 1 patient were hypercholesterolemia (2 pts.), hypertriglyceridemia (4 pts.), neutropenia (3 pts.), lymphopenia (2 pts.) and elevated AST in 2 patients. Lipid lowering agents were used in all patients. Six patients died, all of progressive disease from 1.6–29.9 months following initiation of treatment. The major response rate for the combination of bexarotene and interferon alfa is similar to that for bexarotene alone. Despite the wide confidence intervals that indicate that a small advantage might be missed by not increasing accrual, the clinical usefulness of this combination is limited by the inconvenience of interferon injections. Further trials in CTCL are planned combining bexarotene with other agents, including active cytotoxics.

No abstract

No abstract

No abstract